Statement of work: How do cerebral blood flow (CBF), volume (CBV), and oxygenation (CBO) vary in response to normal and epileptic neuronal activity in the neocortex? The focus of this proposal is to investigate this question in primates in humans using optical imaging techniques combined with electrophysiological and pharmacological studies. Optical imaging of intrinsic optical signals (OI), a technique of focus in these studies, depends on the differential absorption of light by oxy- and deoxy-hemoglobin. OI can selectively measure changes in cortical tissue due to either blood volume or blood oxygenation. Further study of neocortical hemodynamics is important for at least three reasons. First, a better elucidation of the quantitative relationships between cerebral hemodynamics and neuronal activity represents basic knowledge required for a more complete understanding of in vivo brain physiology. Second, identifying the differences in the coupling of cerebral hemodynamics between normal and epileptic activity may shed light on how hemodynamic-related phenomena, such as abnormal changes in blood volume or deoxygenation of neocortical tissue elicited by seizure activity may contribute to tissue atrophy and other pathological aspects of the epileptic brain. Third, quantifying the temporal and spatial relationships between neuronal activity and neocortical hemodynamics is a necessary step towards developing optical imaging as a practical clinical tool for localizing functional and epileptic neocortex in neurosurgical patients. To date, OI has been of limited use in epilepsy research for at least two reasons: i) The problem of interpreting optical signals acquired at the various optical wavelengths has not been fully resolved, and ii) ad hoc or qualitative methods have typically been used for the analysis of optical imaging data, with very little work devoted towards developing rigorous statistical methods necessary for making OI a quantitative technique. A major goal of this project is to resolve these issues. Three specific aims will be addressed in the proposal: Aim 1: To quantify relationships between changes in neuronal activity, CBF, CBV, CBO, and optical imaging; Aim 2: To develop practical statistical methods for modeling and analysis of OI data, and Aim 3: To elucidate the relationships between hemodymanic changes and optical signals in neocortex during ictal and interical activity .